血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂在新型冠状病毒肺炎疫情防控中的应用分析

根据《中国心血管病报告》,中国现患心血管病人数约2.9亿,而大量循证医学证据证实了血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体拮抗剂(ARB)治疗心血管等疾病的价值.ACEI/ARB是肾素-血管紧张素-醛固酮系统(RAAS)的阻滞剂,可上调血管紧张素转换酶2(ACE2)表达水平.而ACE2是新型冠状病毒肺炎(CO...     

ARB与糖尿病肾病

肾素-血管紧张素-醛固酮系统(RAAS)激活在糖尿病肾病(DN)的发生发展中具有重要意义。临床前及临床试验都证明:RAAS阻断药物——管紧张素Ⅱ(AngⅡ)受体拮抗剂(ARB)具有独立于降压效应的多重肾脏保护作用。虽然从各种机制上看ARB可能优于血管紧张素转换酶抑制剂(ACEI),但是目前的研究未能证明ARB在降低尿蛋白、延缓肾功能损害方面比ACEI具有优越性。越来越多的研究证明ACEI合用ARB比单用药物具有更大的保护作用,所以两者合用达到RAAS双重阻断成为新趋势。新的研究还证明ARB肾脏保护作用可能与血管紧张素转换酶(ACE)的基因多态现象相关。     

血管紧张素转化酶抑制剂与受体阻断剂治疗慢性心力衰竭优劣性比较

血管紧张素受体阻断剂(ARB)在受体水平上发挥作用,可更完全地阻断肾素-血管紧张素-醛固酮系统(RAAS),其疗效优于血管紧张素转化酶抑制剂(ACEI).ARB不影响缓激肽系统,因而无类似ACEI的不良反应,安全性可与安慰剂比拟.ARB是否可替代ACEI或与ACEI联合用于慢性心力衰竭(CHF)治疗的探讨,引出CHF患者应首选ACEI还是ARB的争论.本文通过对临床研究证据的回顾,辨别ACEI与ARB对CHF患者治疗的优劣,验证联合用药的疗效.     

血管紧张素受体拮抗剂的真实世界:临床研究证据说明了什么

血管紧张素受体拮抗剂(ARB)在受体水平对肾素-血管紧张素-醛固酮系统(RAAS)发挥抑制作用,因此理论上可能较血管紧张素转化酶抑制剂(ACEI)作用更充分,特别是ARB对血管紧张素(Ang)Ⅱ的阻断作用可能更完全.但上述假设并未获得循证医学证据证实.本文对临床循证研究进行回顾提出,患者在不能耐受ACEI时使用ARB替代治疗可取,但不推荐以ACEI与ARB联合治疗高血压患者.     

ARB与ACEI在糖尿病患者中联合应用的利与弊

在糖尿病的药物治疗中,血管紧张素转换．酶抑制剂（ACEI）是目前广泛用于治疗糖尿病合并高血压、心肌梗死、心力衰竭以及糖尿病肾病的一类药物,可以显著降低病死率、延长寿命、减少心脑血管事件的发生率和减少尿蛋白排泄率。血管紧张素Ⅱ受体拮抗剂（ARB）具有与ACEI相似的作用机制,均作用于肾素-血管紧张素系统（RAS）。     

拮抗血管紧张素与冠状动脉疾病

肾素-血管紧张素系统(RAS)是维持内环境稳定的一个复杂的级联系统,该系统过量表达会导致心血管疾病发生。抑制血管紧张素转化酶(ACE)和血管紧张素Ⅱ的Ⅰ型受体(AT1R)可降低心血管事件发生率和病死率。基于RAS抑制剂对心血管疾病的治疗作用,考虑RAS抑制剂有可能降低心肌血管重建术后缺血性事件的发生。然而,有关心肌血管重建术后冠脉血管再狭窄或再闭塞方面的研究数据并不一致。在多数研究中,血管紧张素转化酶抑制剂(ACEI)并不能降低心肌血管重建术后再狭窄的发生,相反,ACEI甚至与经皮冠脉介入(PCI)治疗后的再狭窄率升高有关;但选择性AT1R拮抗剂能降低PCI后的支架再狭窄。     

血管紧张素转化酶抑制剂与受体阻断齐型治疗慢性心力衰竭优劣性比较

血管紧张素受体阻断剂（ARB）在受体水平上发挥作用，可更完全地阻断肾素-血管紧张素-醛固酮系统（RAAS），其疗效优于血管紧张素转化酶抑制剂（ACEI）。ARB不影响缓激肽系统，因而无类似ACEI的不良反应，安全性可与安慰剂比拟。ARB是否可替代ACEI或与ACEI联合用于慢性心力衰竭（CHF）治疗的探讨，引出CHF患者应首选ACEI还是ARB的争论。本文通过对临床研究证据的回顾，辨别ACEI与ARB对CHF患者治疗的优劣，验证联合用药的疗效。     

血管紧张素受体阻断剂用于糖尿病治疗的作用研究

近年来多项临床研究提示血管紧张素Ⅱ受体拮抗剂(ARB)不仅能降低血压,延缓糖尿病慢性并发症的发生,尚具有保护肾脏及心血管系统及降低糖尿病发生率的作用。     

血管紧张素Ⅱ受体阻断剂治疗急性心肌梗死:新证据和新争议

血管紧张素转化酶抑制剂(ACEI)抑制肾素-血管紧张素-醛固酮系统(RAAS)已经成为治疗急性心肌梗死的基石．血管紧张素Ⅱ受体阻断剂(ARB)能更完全地阻断血管紧张素Ⅱ的作用。但是,ARB对急性心肌梗死患者的预后影响是否优越于ACEI,ACEI联合ARB的治疗策略,是否能获得更大的益处均存在争议。     

血管紧张素转换酶抑制剂联合血管紧张素II受体阻滞剂治疗糖尿病肾病的临床研究

目的:观察血管紧张素转换酶抑制剂(ACEI)联合血管紧张素II受体阻滞剂(ARB)治疗糖尿病肾病是否优于单独用药治疗,以探讨治疗糖尿病肾病更有效的治疗方法。方法:筛选72名病人,建立3个观察组:ACEI组(ACEI代表药物为蒙诺)、ARB组(ARB代表药物为代文)、ACEI+ARB组(蒙诺联合代文);疗程8周,治疗前后检测24 h尿蛋白定量。结果:3个治疗组治疗前尿蛋白定量无统计学差异(P>0.05),具有可比性;每个治疗组治疗后24 h尿蛋白定量减少;与单独用药组相比,联合用药组尿蛋白显著降低。结论:无论是单用蒙诺或代文,还是联合蒙诺及代文,均可有效降低尿蛋白;蒙诺组与代文组治疗效果相当。而联合用药组治疗效果明显优于单独用药组。     

ARB与ACEI联合治疗血液透析患者慢性心力衰竭疗效观察

目的观察联合应用血管紧张素Ⅱ受体抑制剂(ARB)与血管紧张素转化酶抑制剂(ACEI)和单用ACEI治疗血液透析患者慢性心力衰竭(简称慢性心衰)的疗效比较。方法 42例临床确诊为慢性心力衰竭的血液透析患者分为两组,A组单用ACEI治疗20例,B组联合应用ARB与ACEI治疗22例。结果治疗6个月后A组左室射血分数(LVEF)、心脏指数(CI)、心血管病事件发生率及心血管病死亡率分别为49.20±3.27、(4.11±0.35)mL/m2、45%、5%;B组分别为53.36±4.27、(4.43±0.52)mL/m2、22.7%、4.5%。治疗1年后A组LVEF、CI、心血管病事件发生率、心血管病死亡率分别为54.20±2.84、(4.36±0.33)mL/m2、30%、10%;B组分别为61.68±3.50、(5.19±0.30)mL/m2、13.6%、4.5%。结论联合应用ARB与ACEI治疗血液透析患者慢性心衰,在改善心功能疗效方面更优于单用ACEI组,虽然在心血管病事件及心血管病死亡方面比对照组呈现较好的下降趋势,但两组差异无统计学意义。可能需要延长观察时间以判断心血管的长期预后。     

缬沙坦联合贝那普利对慢性肾小球肾炎蛋白尿降低和肾功能保护作用的临床研究

目的:观察血管紧张素转化酶抑制剂(ACEI)联合血管紧张素受体拮抗剂(ARB)治疗慢性肾小球肾炎的疗效。方法:将65例慢性肾小球肾炎患者随机分为三组:ACEI组、ARB组和联合组。ACEI组应用贝那普利,ARB组应用缬沙坦,联合组联合应用贝那普利及缬沙坦。观察治疗后3,6,9个月的相关指标变化。结果:经过9个月治疗后,三组患者24 h尿蛋白及血压显著下降(P<0.05);肾功能及血钾无明显变化(P>0.05);不良反应小。三组中联合组有最强的减少尿蛋白和降低舒张压作用(P<0.05),而在改善肾功能、血钾波动及不良反应方面,三组间差异无统计学意义(P>0.05)。结论:联合药物治疗慢性肾小球肾炎有更强的降低蛋白尿和舒张压的作用。     

血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂在慢性心力衰竭治疗中的应用

心力衰竭是多种心脏病的最终死亡原因,阻断肾素-血管紧张素-醛固酮系统(renin angiotensin aldosterone system,RAAS)是减慢心力衰竭病变进展的主要策略。血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitors,ACEI)和血管紧张素受体拮抗剂(angiotensin receptor blockers,ARB)是目前最常用的阻断RAAS的药物。本文对慢性心力衰竭评估,以及ACEI和ARB在慢性心力衰竭治疗中的应用进行综述。     

Therapeutic potential of ACE inhibitors for the treatment of hypertension in Type 2 diabetes

Type 2 diabetes mellitus is associated with hypertension. If untreated, hypertension has a major impact on the clinical course of Type 2 diabetes and its vascular complications. In this review, we discuss rationale for the use of ACE inhibitors (ACEI) in hypertensive Type 2 diabetic patients and compare those theoretical assumptions with results of recent major clinical trials. Furthermore, possible directions for future clinical and experimental research are outlined. The RAS and its effector angiotensin II are important players in a number of cardiovascular and renal disorders. Recent evidence suggests that RAS and factors functionally linked to RAS are activated in Type 2 diabetes. Therefore, there is a theoretical basis for the use of ACEI in the treatment of hypertension in diabetic patients. Some recent studies reported superior outcome in patients treated with ACEI-based antihypertensive regimens compared with non-ACEI based treatments in reducing the risk of macrovascular disease (CAPPP, FACET, ABCD) or both micro- and macrovascular complications in Type 2 diabetes (HOPE). However, at least two of the large prospective studies discussed in this review (UKPDS 38, HOT), supported by results from previously published SHEP study, have recently suggested that the degree of reduction of blood pressure, rather than the choice of a particular class of antihypertensive agent, is associated with decreased risk of cardiovascular events. Studies focusing on renal end-points suggest that ACEI have a superior antiproteinuric effect than the other agents. However, whether ACEI are more nephroprotective, as assessed by the rate of decline in renal function, still remains to be elucidated. Despite promising results from recent trials, large numbers of patients progress despite ACEI treatment. Incomplete inhibition of the RAS may underlie this phenomenon. Treatment strategies that could enhance the degree of RAS inhibition represent one possible direction for clinical research in the near future. However, it is unlikely that the course of such a complex syndrome as Type 2 diabetes could be dramatically changed by just one class of antihypertensive agents. This goal is more likely to be achieved by multifactorial intervention, reflecting the complexity of metabolic syndrome. ACEI should be viewed as an important, but not the only, part of this complex approach.     

吡格列酮对早期糖尿病肾病的影响

目的观察吡格列酮对早期糖尿病肾病(DN)微量白蛋白尿(MAU)的影响。方法102例早期DN患者.将其随机分为2组。在常规降糖、有高血压者应用血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体阻滞剂(ARB)降压的基础上,治疗组加用吡格列酮15mg/d口服,连用12周。观察两组患者治疗前、后MAU、糖化血红蛋白(HbA1 c)、血压、血肌酐(SCr)变化。结果治疗组患者治疗前、后MAU均值差别有显著性意义(P<0.01),对照组患者治疗前、后MAU均值差别也有意义(P<0.01),治疗后治疗组与对照组MAU均值差别也有意义;治疗组中血压正常者治疗前、后的MAU在治疗组差别有意义,在对照组差别无显著性意义,治疗后治疗组与对照组MAU均值差别也有意义;伴高血压者治疗前、后的MAU在治疗组差别有意义,在对照组差别有意义,治疗后治疗组与对照组MAU均值差别也有意义。结论吡格列酮可明显减少早期糖尿病肾病患者的MAU,并与ACEI、ARB有协同保护肾脏作用。     

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in women of childbearing age: risks versus benefits

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are effective and widely used antihypertensive drugs. Exposure to these agents is known to be harmful to the fetus in the second and third trimesters of pregnancy. Concerns have also been raised about the risk of congenital malformations if ACEIs or ARBs are taken during the first trimester of pregnancy. The evidence to date, however, is conflicting and observed malformations may be due to confounders such as undiagnosed diabetes or maternal obesity, other antihypertensive medications or the hypertension itself. Nonetheless, in women who become pregnant while taking an ACEI or ARB, the drug should be stopped as soon as possible. In women with chronic kidney disease and proteinuria, it may be appropriate to continue taking an ACEI or ARB until the pregnancy is confirmed because of the significant benefit to their kidney function and the lower fertility rate in these patients.     

厄贝沙坦对2型糖尿病肾病微量白蛋白尿治疗的临床观察

目的:观察厄贝沙坦对2型糖尿病肾病患者尿微量蛋白的作用;方法:64例符合纳入标准患者,随机分为厄贝沙坦治疗组34例,对照组30例,观察时间24周.结果:两组之间血压变化无统计学意义(P=0.276),尿微量白蛋白差异有统计学意义(P＜0.05).结论:厄贝沙坦具有独立于降压作用之外的减少糖尿病肾病尿微量白蛋白作用.     

Role of renin angiotensin system inhibitors in cardiovascular and renal protection: a lesson from clinical trials

Beneficial effects of angiotensin converting enzyme inhibitors (ACEI) and angiotensin type 1 receptor (AT1) blockers in patients with cardiovascular and renal diseases have been clearly demonstrated in numerous large outcomes studies. In patients with heart failure (HF), ACEI have been shown to reduce overall mortality, mortality from cardiovascular causes, to increase life expectancy, as well as to preserve the renal function (CONSENSUS, SAVE, TRACE, AIRE, AIREX, CATS trials). In addition, in the PROGRESS study ACEI substantially decreased the risk of stroke and transient ischemic attacks in patients with cerebrovascular disorders. The HOPE and EUROPA studies confirmed that long term therapy with ACEI provides significant survival benefit in patients with broad range of atherosclerotic cardiovascular diseases. After these large and well designed clinical studies, ACEI have become standard therapy for routine secondary prevention in all patients with cardiovascular diseases, unless contraindicated. AT1 receptor blockers have been recently added to the cardiovascular therapeutic armamentarium. They are believed to provide additional protection by inhibition of locally synthesized angiotensin II on the level of AT1 receptor. The ELITE II, ValHeFT and CHARM studies have shown that AT1 receptor blockers are equally effective as ACEI in reduction of mortality and morbidity in patients with HF. Importantly, they may be used together with ACEI, or as alternative treatment in ACEI intolerant patients. Renal protection is another important effect of both ACEI and AT1 blockers that has been confirmed in several large clinical trials. The North American Microalbuminemia Study group and EUCLID group demonstrated significant reduction in progression of diabetic nephropathy in patients with insulin dependent diabetes mellitus (IDDM) treated with ACEI. AT1 receptor blockers are mainly studied in the non-insulin dependent diabetes mellitus (NIDDM) nephropathy. Four recent clinical trials (IRMA-2, DETAIL, RENAAL and IDNT) examined the effect of AT1 receptor blockers in patients with NIDDM nephropathy. These studies confirmed the beneficial effect of AT1 receptor blockers in patients with NIDDM nephropathy that was extended beyond the blood pressure reduction. Ongoing studies (ONTARGET, TRANSCEND and PROTECTION) should provide us with additional insights about cardiovascular, renal and other end-organ protective effects of these therapeutics.